Pseudomonas aeruginosa (Pa) is a major cause of morbidity and mortality in patients with nosocomial pneumonia and patients with cystic fibrosis. Although usually considered an extracellular pathogen, Pa may be able to enter respiratory epithelial cells in order to avoid host defenses. Caveolae are lipid rich domains present on the plasma membranes of a wide range of cell types including the alveolar epithelium that can function as an alternative pathway of endocytosis. We hypothesize that the virulence of Pa may be in part due to its ability to live intracellularly within the alveolar epithelium. Pa may co-opt the pathway of caveolae-mediated endocytosis as a mechanism invading type I pneumocytes. This work is important because interventions aimed at reducing the morbidity and mortality of Pa must be refined by a better knowledge of the mechanisms by which Pa avoids host defenses. Specific Aims: I) Expose primary cell cultures of rat type I-like pneumocytes to several strains of Pa to screen for the ability of Pa to invade the alveolar epithelium. 2) Determine the role of caveolae in the uptake of Pa by examining the cellular invasion of type I-like pneumocytes by previously identified invasive strains of Pa. 3) Examine the specific role of caveolin-I in the endocytosis of invasive strains of Pa.